Extraosseous ^99mTc-methylene diphosphonate uptake on bone scan: Unusual scenario

INTRODUCTION

The purpose of bone scintigraphy is to locate areas of new bone formation within the skeleton. This is useful in imaging reaction of bone to tumor, fracture, and infection. The procedure is most commonly performed with ^99mTc-MDP. These compounds accumulate rapidly in bone, and by 2-6 h after injection, about 50% of the injected dose is retained the skeletal system. The extraosseous uptake is often an unexpected finding on the bone scan. Extraosseous radioactivity outside of the expected biodistribution is often seen on ^99mTc–methylene diphosphate (MDP) bone scintigraphy, and accurate interpretation needs an understanding of the mechanisms underlying this uptake and knowledge of the possible causes, depending on the site or structure involved.

CASE REPORT

A 32-year-old male patient, being evaluated for difficulty in walking and sitting with pain in whole back since 2 months and clinical suspicion of unknown primary. Magnetic resonance imaging (MRI) cervico-dorso-lumbar spine showed altered marrow signal intensities on T1- and T2-weighted images in multiple cervical, dorsal and lumbar vertebrae and altered signal intensity in sacrum and both iliac bones suggestive of marrow infiltration. Liver involvement was also noted on MRI. The patient underwent ^99mTc-methylene diphosphonate (MDP) whole body bone scan 3 h after intravenous administration of 740 MBq (20 mCi) of ^99mTc-MDP. Standard whole body anterior and posterior sweep images were acquired on a dual head single-photon emission computed tomography-computed tomography gamma camera using a low energy high-resolution collimator. Images were acquired on a 512 × 1024 matrix with a scan speed of 12 cm/min. Bone scan revealed increased tracer uptake in skull, sternum, multiple ribs bilaterally, sacrum and pelvis with photopenic areas and multiple cervical, dorsal and lumbar vertebrae with photopenic areas in L1, L2, and L5 vertebrae. Scan findings were suggestive of multiple skeletal metastases. Patchy soft tissue tracer uptake was also noted in the liver and spleen [Figure 1].

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Figure 1 Bone scan reveals increased tracer uptake in skull, sternum, multiple ribs bilaterally, sacrum and pelvis with photopenic areas and multiple cervical, dorsal and lumbar vertebrae with photopenic areas in L1, L2 and L5 vertebrae and patchy soft tissue tracer uptake in the liver and spleen

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The patient's blood profile was deranged in the form of raised total serum bilirubin - 2.98 mg/dl, serum glutamic oxaloacetic transaminase - 366 U/L, serum glutamic pyruvic transaminase - 98 U/L, serum alkaline phosphatase - 761 U/L, serum lactate dehydrogenase - 1687 U/L, and serum gamma-glutamyltransferase - 669 U/L.

Another patient, a 25-year-old male patient, being evaluated for headache and vomiting for the past 3 months. The contrast-enhanced MRI brain showed a large space occupying lesion in the posterior fossa (hyperintense on T2) with contrast enhancement in the superior cerebellar cistern and another small similar lesion seen in the anterior part of temporal lobe. MRI findings were suggestive of medulloblastoma. The patient underwent ^99mTc-MDP whole body bone scan 3 h after intravenous administration of 740 MBq (20 mCi) of ^99mTc-MDP for the detection of any skeletal metastases using the same imaging parameters. Bone scan findings did not reveal any abnormal focal skeletal lesion [Figure 2]. However, there was diffuse uptake of tracer in both liver as well as spleen. The patient's blood profile showed Hb 17.2 g/dl, TLC 21 × 103 cells/µL, platelets 126 × 103/cmm, serum creatinine 0.7 mg/dl, and serum BUN 15 mg/dl.

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Figure 2 Bone scan findings did not reveal any abnormal focal skeletal lesion, but there is diffuse uptake of tracer in liver and spleen

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Other bone scans done on that same day revealed absolutely normal tracer distribution in the skeleton with no abnormal soft tissue tracer uptake. Thus, the chance of radiopharmaceutical mispreparation or contamination was ruled out.

DISCUSSION

Tc-99m-MDP bone scan is the most commonly performed nuclear medicine procedure in most of the nuclear medicine departments worldwide. Usually 50–60% of Tc-99m-MDP is localized in the bones and the rest is cleared by the kidneys. The benign and pathological lesions of the bones are diagnosed by increased uptake of the tracer by the lesions due to various reasons such as increased blood flow, increased osteoid formation or increased mineralization.[1]

Physiological uptake of Tc-99m-MDP is seen in osseous structures, kidney, and bladder. A wide spectrum of nonosseous disorders, i.e., neoplastic, hormonal, inflammatory, ischemic, traumatic, excretory, and artefactual entities, demonstrate abnormal soft tissue uptake of Tc-99m-MDP.[2] On delayed images an extraosseous abnormal tracer uptake can be seen in soft tissue, such as stomach, spleen, liver, muscles or lungs, which is often an unexpected finding. There are many causes for such an uptake although the responsible pathological entity is not always clear. Some known mechanisms resulting in extra skeletal uptake include: Normal variants; radiopharmaceutical preparation; interfering medications; extracellular fluid expansion; altered calcium metabolism; increased calcium content of tissues; hyperemia; altered vascular permeability; presence of iron deposits; ion exchange; adsorption onto immature collagen; and binding to denatured proteins or enzyme receptors.[3]

Focal or diffuse liver uptake has been seen sometimes in patients undergoing bone scan. Focal uptake is more frequent than diffuse hepatic activity. Focal tracer uptake is usually seen in the case of hepatic metastasis. Diffuse liver uptake can be due to numerous causes such as residual radioactivity from previous colloid scans, excessive hydrolyzed-reduced ^99mTc-MDP forming radio colloids, injection of radio iodinated contrast medium following MDP injection, excessive aluminum ion from generator eluate, hepatic necrosis, iron overload, amyloid or metastatic calcification of the tracer, or severe hepatic necrosis.[4] Diffuse and intense hepatic uptake, followed by hypoxia due to respiratory failure, along with the development of hepatic necrosis, has also been reported on bone scan.[5]

Splenic uptake has been seen in the bone scan of patients with sickle-cell disease as a result of splenic infarction and subsequent calcification.[6] Splenic accumulation of the tracer is also observed in patients with alcoholic cirrhosis of the liver, hemolytic anemia, and hemochromatosis resulting from alcohol abuse, both of which are thought to be related to the diffuse splenic uptake observed. When diffuse splenic accumulation by Tc-99m-hydroxy diphosphonate/methylene diphosphonate (Tc-99m-HDP/MDP) is seen, the existence of alcoholic hepatopathy might be considered.[7] The increased ^99mTc-MDP activity in the liver and spleen can also be an effect of gadolinium-containing MRI contrast.[8] This could be the reason for hepatic and splenic uptake in the second patient.

Diffuse uptake of MDP is also associated with chronic renal failure and hyperparathyroidism. In hypercalcemic conditions, the solubility product for calcium and phosphate may be exceeded (Ca2⁺ [mg/dL] and PO43⁻ [mg/dL] >60),[9] causing a precipitation of calcium salts in the extracellular space that may be reflected by extraosseous uptake of ^99mTc-MDP. The uptake of ^99mTc-MDP is by adsorption to the surface of the hydroxyapatite crystal. In soft tissue, calcium localizes through a limited number of common pathways. It is thought that calcium ion binds to phospholipids present in membrane bound vesicles, phosphatases generate phosphate groups, which in turn bind to the calcium, and the cycle is repeated until local concentrations are elevated and crystals begin to form. This results in chemisorption of the MDP on to the surface of the calcium salts.[10]

Bone scan is a test primarily used to see skeletal abnormalities; however, nonosseous findings are occasionally present on the images. To determine the significance of these findings, nuclear medicine personnel must be well trained to recognize the various patterns of nonosseous uptake and understand their mechanism.

CONCLUSION

The need for awareness of the pathophysiological causes of extraosseous uptake is of much critical clinical relevance in a patient undergoing bone scan. Although alterations in radiopharmaceutical preparation and biodistribution are important considerations to be thought of in case of extraosseous tracer uptake, proper knowledge of the pathophysiology behind clinical condition is very important for accurate reporting. Recognition of abnormalities will reduce errors and provide important clinical information.